Diagnosis of hereditary retinal degenerative diseases

Abstract

The invention generally provides a method of diagnosing in a human subject an increased likelihood of developing or transmitting to future generations a disease in which a mutant form of a human photoreceptor protein is a causative agent. The method involves analyzing the DNA of the subject to determine the presence or absence of a mutation in a gene for a photoreceptor protein.

What is claimed is: 
     
       1. A method of diagnosing in a human subject an increased likelihood of developing or transmitting to future generations a disease in which a mutant form of a human photoreceptor protein is a causative agent, said method comprising, analyzing the DNA of said human subject to determine the presence or absence of a mutation in a gene for a protein selected from the group consisting of rhodopsin, retinal degeneration slow (RDS) protein, and the β-subunit of retinal rod cGMP phosphodiesterase, the presence of such a mutation indicating an increased likelihood of developing or transmitting to future generations a disease in which a mutant form of a human photoreceptor protein is a causative agent.   
     
     
       2. The method of claim 1, wherein said DNA is analyzed by amplifying said DNA and identifying said mutation in said amplified DNA. 
     
     
       3. The method of claim 1, wherein said analyzing the DNA of said human subject comprises identifying a single strand conformation polymorphism. 
     
     
       4. The method of claim 1, wherein said analyzing the DNA of said human subject comprises DNA sequencing. 
     
     
       5. A probe or primer consisting of a purified single-stranded oligonucleotide, said oligonucleotide being of 10-50 nucleotides in length and containing a region the sequence of which is identical to the sequence of a six-nucleotide, single-stranded segment of a gene encoding a mutant form of the β-subunit of retinal rod cGMP phosphodiesterase, said segment comprising part or all of a mutation characterizing said mutant form of said gene. 
     
     
       6. The probe or primer of claim 5, wherein said oligonucleotide is DNA. 
     
     
       7. The probe or primer of claim 5, wherein said mutation comprises a change in the codon encoding glutamine 298 of said β-subunit of retinal rod cGMP phosphodiesterase. 
     
     
       8. The probe or primer of claim 5, wherein said mutation comprises a change in the codon encoding arginine 531 of said β-subunit of retinal rod cGMP phosphodiesterase. 
     
     
       9. The probe or primer of claim 5, wherein said mutation comprises a change in the codon encoding proline 496 of said β-subunit of retinal rod cGMP phosphodiesterase. 
     
     
       10. The probe or primer of claim 9, wherein said change is a deletion of a nucleotide from said codon 496. 
     
     
       11. The probe or primer of claim 5, wherein said mutation comprises a change in the codon encoding histidine 557 of said β-subunit of retinal rod cGMP phosphodiesterase. 
     
     
       12. The method of claim 1, wherein said analyzing the DNA of said human subject comprises: (a) providing a probe or primer consisting of a purified oligonucleotide, said oligonucleotide being of 10-50 nucleotides in length and containing a region the sequence of which is identical to the sequence of a six-nucleotide segment of a gene encoding a mutant form of a protein selected from the group consisting of rhodopsin, retinal degeneration slow protein, and the β-subunit of retinal rod cGMP phosphodiesterase, said segment comprising part or all of a mutation characterizing said mutant form;   (b) exposing said probe or primer to said DNA of said human subject; and   (c) detecting hybridization of said probe or primer to said DNA, thereby determining the presence of said mutation in said gene.   
     
     
       13. The method of claim 12, wherein said human subject is a fetus or a patient. 
     
     
       14. The method of claim 12, wherein said method is used to detect a genetic predisposition to develop a hereditary retinal degenerative disease. 
     
     
       15. The method of claim 1, wherein said analyzing the DNA of said human subject comprises (a) providing a probe or primer consisting of a purified oligonucleotide, said oligonucleotide containing a region the sequence of which is identical to the sequence of a six-nucleotide segment of a gene encoding a mutant form of a protein selected from the group consisting of rhodopsin, retinal degeneration slow protein, and the β-subunit of retinal rod cGMP phosphodiesterase, said segment comprising part or all of a mutation characterizing said mutant form;   (b) combining said probe or primer with a second primer and said DNA of said human subject, under conditions permitting amplification of a DNA template comprising said mutation in said gene; and   (c) detecting amplification of said DNA template, thereby determining the presence of said mutation in said gene.   
     
     
       16. The method of claim 15, wherein said human subject is a fetus or a patient. 
     
     
       17. The method of claim 15, wherein said method is used to detect a genetic predisposition to develop a hereditary retinal degenerative disease.